History and challenges of multi-organ allocation in the United States: A systematic review

Current multi-organ candidates are prioritized primarily based on single-organ risk scores. Once the primary organ is allocated, the secondary organ follows to the same recipient, resulting in waitlisted single-organ candidates being skipped in allocation. Our previous work examined the ethical and statistical alignment of single-organ risk scores. Here, we aim to extend our analysis to multi-organ transplantation policies in the United States, surveying the current state of multi-organ candidate prioritization and the challenges of conducting high-quality research in multi-organ transplantation. We systematically searched PubMed for published literature on the allocation of all multi-organ pairs involving the liver, kidney, lungs, and heart. After screening based on our inclusion and exclusion criteria, we identified 126 articles to include in this review. These include 31 articles for Heart-Lung, 24 for Heart-Kidney, 52 for Liver-Kidney, and 19 for Liver-Heart transplantation. We did not discuss the remaining organ pairs due to insufficient literature to provide a balanced analysis. Provider-, center-, and region-dependent variations exist in multi-organ practices due to evolving national guidelines and a lack of standardized institutional protocols for candidate evaluation and listing. The use of single-organ risk scores in multi-organ allocation has not been statistically validated, therefore raising concerns about applicability. Multi-organ transplant research relies heavily on single-center reports, case studies, and registry-based analyses. The frequent re-use of national registry data limits the novelty and reliability of multi-organ research. We encourage future efforts to consider exploratory, prospective, and perhaps randomized-controlled trials to advance understanding and strengthen the evidence base in multi-organ transplantation.